Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs

Abstract

Some effects of parasitism, endotoxaemia or sepsis can be mitigated by provision of extra protein. Supplemented protein may encompass a metabolic requirement for specific amino acids (AA). The current study investigates a method to identify and quantify the amounts of AA required during inflammation induced by an endotoxin challenge. One of each pair of six twin sheep was infused in the jugular vein for 20 h with either saline (control) or lipopolysaccharide (LPS, 2 ng/kg body weight per min) from Escherichia coli. Between 12 and 20 h a mixture of stable isotope-labelled AA was infused to measure irreversible loss rates. From 16 to 20 h all sheep were supplemented with a mixture of unlabelled AA infused intravenously. Blood samples were taken before the start of infusions, and then continuously over intervals between 14 and 20 h. At 20 h the sheep were euthanised, and liver and kidney samples were taken for measurement of serine-threonine dehydratase (SDH) activity. LPS infusion decreased plasma concentrations of most AA (P < 0·05; P < 0·10 for leucine and tryptophan), except for phenylalanine (which increased P = 0·022) and tyrosine. On the basis of the incremental response to the supplemental AA, arginine, aspartate, cysteine, glutamate, lysine (tendency only), glycine, methionine, proline, serine and threonine were important in the metabolic response to the endotoxaemia. The AA infusion between 16 and 20 h restored the plasma concentrations in the LPS-treated sheep for the majority of AA, except for glutamine, isoleucine, methionine, serine and valine. LPS treatment increased (P < 0·02) SDH activity in both liver and kidney. The approach allows quantification of key AA required during challenge situations.Key words: Endotoxin lipopolysaccharide: Amino acids: Irreversible loss rate: Serine-threonine dehydratase: SheepThe protein and amino acid (AA) demands of animals for normal physiological states (e.g. growth, pregnancy and lactation) are now well characterised, especially for pigs and poultry (1) and with progress made in ruminants (2) . These requirements are altered, however, in response to injury, infection and parasitic challenge. In many cases, impact of these challenges can be ameliorated and the rate of recovery improved by provision of additional protein in the diet (3)(4)(5)(6) . Often, however, the amount of protein required is not known, with consequences for both animal performance and farm economics.More importantly, protein per se may not be required, but instead the metabolic responses to the challenge may increase the demand for specific AA. For example, practical and theoretical arguments have been presented for additional arginine in cardiovascular and pulmonary disorders (7)(8)(9)(10) , for cysteine (11) , leucine (12) and threonine (13) in sepsis, for glutamine in endotoxaemia (10) , and for phenylalanine to support acutephase protein synthesis (14) . In other situations, combinations of AA have been proposed (10,15,16) . Obviously different stages of injury, infection or recover...

Post-ruminal branched-chain amino acid supplementation and intravenous lipopolysaccharide infusion alter blood metabolites, rumen fermentation, and nitrogen balance of beef steers1

“…Hoskin et al (2016) eloquently described that individual AA concentrations in the plasma pool are reflective of multiple factors that alter inflow (intestinal absorption, endogenous protein catabolism, de novo synthesis of nonessential AA) and outflow (extraction for protein synthesis, oxidation of AA), and that simple changes in plasma concentrations of an AA may not necessarily indicate a metabolic need specific for that AA. The metabolic demand of a different AA could cause an AA imbalance, thereby altering the plasma concentration of a specific AA indirectly (Hoskin et al, 2016). Nevertheless, the following are possible metabolic mechanisms that could explain some of the observed effects of LPS infusion on specific plasma AA concentrations in this study.…”

“…Decreases in plasma Trp concentrations may also be reflective of an increase in the catabolism of Trp via the kynurenine pathway during inflammation (Le Floc'h and Seve, 2007;Hoskin et al, 2016), and decreases in plasma Thr concentrations could be in response to the inflammatory demand for increased synthesis of mucosal proteins in addition to acutephase proteins (Faure et al, 2006(Faure et al, , 2007. However, Hoskin et al (2016) also observed increased hepatic serine-threonine dehydratase activity in LPSchallenged lambs, which could be indicative of increased Thr catabolism. A decrease in plasma Tyr concentrations of steers in response to LPS infusion could also be related to the use of this AA as the immediate precursor for the synthesis of dopamine and the catecholamine hormones (epinephrine and norepinephrine), which increase in response to LPS in cattle (Li et al, 2007;Burdick et al, 2011).…”

“…These responses are perhaps not surprising considering the large concentration of aromatic AA and Thr found in acute-phase proteins (Reeds et al, 1994;Reeds and Jahoor, 2001). Decreases in plasma Trp concentrations may also be reflective of an increase in the catabolism of Trp via the kynurenine pathway during inflammation (Le Floc'h and Seve, 2007;Hoskin et al, 2016), and decreases in plasma Thr concentrations could be in response to the inflammatory demand for increased synthesis of mucosal proteins in addition to acutephase proteins (Faure et al, 2006(Faure et al, , 2007. However, Hoskin et al (2016) also observed increased hepatic serine-threonine dehydratase activity in LPSchallenged lambs, which could be indicative of increased Thr catabolism.…”

Short communication: Effects of meloxicam administration on protein metabolism and growth performance in transported Jersey calves

“…Therefore, it is plausible that the metabolic demand for AA to support various stress response-related functions, including haptoglobin synthesis, was not sufficiently higher in CON than in MEL calves to result in differences in the rate of skeletal muscle protein breakdown in our study. In addition to dietary supply, systemic AA concentration is determined by the processes of protein synthesis and breakdown, and de novo AA synthesis and oxidation (Waggoner et al, 2009;Hoskin et al, 2016). Plasma concentrations of Asn, Asp, Cit, Glu, Lys, Met, Ser, and Trp were greater (P ≤ 0.04), and those of Arg, Gly, Pro, and Thr tended to be greater (0.07 ≤ P ≤ 0.09) in MEL than in CON calves at 96 h after transport (Table 2).…”

“…The higher MR intake for MEL compared with CON calves could account for the greater plasma AA concentrations in our study. Although information for transported calves is still lacking, pro-inflammatory and APP reactions induced in cattle and sheep using an endotoxin challenge resulted in a decrease in the plasma concentration of several AA, including Asn, Glu, Lys, and Phe (Waggoner et al, 2009;Hoskin et al, 2016). This is attributed to increased use of systemic AA to support various stress response-related functions, including hepatic APP synthesis and gluconeogenesis.…”